The embryonic development of and the maintenance of healthy adult of a eukaryotic organism depends on faithful mitosis. During mitosis, the duplicated genetic materials were transmitted into two daughter cells. Errors in mitosis will lead to aneuploidy daughter cells, and will promote tumorgenesis and other diseases. The morphology and structure of cells changed sharply during mitosis, although the time span of mitosis is short comparing to the whole cell cycle. The course of mitosis is highly dynamic and is under the fine regulation of mitotic kinases (e.g. CDK1, PLK1, Aurora A/B), protein phosphotase and Ubiquitin E3 ligase APC/C. The spindle assembly checkpoint (SAC) is a surveillance mechanism to safeguard the faithful chromosome segregation. Until all chromosomes achieved correct kinetochore-microtubule attachment, the cells enter anaphase due to the satisfaction of SAC. We are interested on the following scientific questions:
The molecular composition, assembly, structure and function of kinetochore;
The establishment of stable kinetochore-microtubule attachment;
Functions and regulations of mitotic kinases;
Functions and regulations of motor protein involved in mitosis;
The signaling pathway and molecular mechanism of SAC;
Chemical Biology and Drug Action
Numerous proteins temporally and spatially have important roles in intracellular transport or cell division. Kinesins are a family of molecular motor proteins that power cargo movements on microtubules using ATP. As the most important post-translational modification of proteins, phosphorylation plays essential roles in all aspects of biological processes. We focus on chemical biological studies of kinesins and kinases over the past 16 years, which have allowed the development of specific chemical inhibitors to probe the precise functions of individual motor proteins and kinases in space and time. Modern drug discovery involves the identification of screening hits, medicinal chemistry and optimization of those hits to increase the affinity, selectivity, efficacy/potency, metabolic stability, and oral bioavailability. Once a compound that fulfills all of these requirements has been identified, it will begin the process of drug development prior to clinical trials.
Cell Dynamics and Extracellular Cues
The extracellular matrix (ECM) is fundamental to the form and function of soft connective tissues. Cells within these tissues establish the ECM during development, maintain it in health, remodel it during adaptations and repair it in response to disease and injury. Interactions between cells and their extracellular matrix regulate a wide variety of cellular processes of crucial importance for cell behavior such as migration, growth, differentiation, embryonic development, immune responses, cell death/survival ,cell-cell adhesion and so on.
Our lab focus on proteins which provide a platform for the transmission of signals in responses to extracellular cues, such as Ezrin, ARF6, ACAP4. Meanwhile, These proteins provide a regulated linkage between the membrane and the underlying cytoskeleton. We devote to utilize cell biology technology, molecular biology technology, advanced microscopy techniques (deconvolution microscopy, super resolution microscopy technology) to revealthe mechanism of Cell-ECM crosstalk and Cytoskeleton–ECM functional relevance.We also develop the proteomics technology to discover the function of protein post-translational modification (such as phosphorylation and acetylation) in Extracellular Cues Dynamics.